| dc.contributor.advisor | Nave, Klaus-Armin Prof. Dr. | |
| dc.contributor.author | Restrepo Arango, Alejandro | |
| dc.date.accessioned | 2022-08-08T12:35:08Z | |
| dc.date.available | 2023-06-18T00:50:11Z | |
| dc.date.issued | 2022-08-08 | |
| dc.identifier.uri | http://resolver.sub.uni-goettingen.de/purl?ediss-11858/14201 | |
| dc.identifier.uri | http://dx.doi.org/10.53846/goediss-9398 | |
| dc.language.iso | eng | de |
| dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
| dc.subject.ddc | 570 | de |
| dc.title | Neurovascular coupling in a central nervous system white matter tract | de |
| dc.type | doctoralThesis | de |
| dc.contributor.referee | Nave, Klaus-Armin Prof. Dr. | |
| dc.date.examination | 2022-06-20 | de |
| dc.description.abstracteng | Neurovascular coupling is the process by which blood vessels dilate upon increased
neuronal activity. It has been extensively studied in the murine grey matter and there are
several models explaining possible molecular and cellular pathways that communicate
neuronal needs to the vascular system. However, neurovascular coupling in the white
matter, which represents half of the human brain, has been constantly overlooked. I used
the optic nerve as a model system to study neurovascular coupling in white matter. In the
optic nerve, spiking axons release glutamate into the periaxonal space. Glutamate activates
NMDA receptors located in the myelin membrane, and oligodendrocytes increase their
glycolytic metabolism to support the ATP production of the underlying axon. This process
of neurometabolic coupling requires that the vascular system matches the axonal activity
and increases the availability of glucose and oxygen. How this is done in the white matter
remains elusive. My experiments show that axonal activity induces a small vessel dilation
which is both prolonged and sustained for more than 20 min after the end of the stimulation.
Pharmacological inhibition suggests that the electrically-evoked dilation is mediated by the
prostaglandin E2 receptor EP4 and can be modulated by oxygen concentration. These
experiments demonstrate that some of the principles that govern the response of the grey
matter are also in place for the white matter. By using neurogenetics, I show that the vessel
dilation is partially mediated by oligodendroglial NMDA receptors, supporting the published
white matter neurometabolic model. A preliminary study using task-based fMRI immediately
followed by a long resting-state fMRI shows a positive and strong BOLD signal in the corpus
callosum during the resting state only when the task was performed. These data suggest
that white matter neurovascular coupling is a process that mainly happens after the
neuronal activation has finished, hinting that neurovascular coupling in white matter is
necessary to replenish the energy stores that have been used, and not to support the axonal
activity. | de |
| dc.contributor.coReferee | Boretius, Susann Prof. Dr. | |
| dc.contributor.thirdReferee | Raimundo, Nuno Dr. | |
| dc.subject.eng | Neurovascular coupling | de |
| dc.subject.eng | White matter | de |
| dc.subject.eng | Axo-glia communication | de |
| dc.subject.eng | Optic nerve | de |
| dc.identifier.urn | urn:nbn:de:gbv:7-ediss-14201-4 | |
| dc.affiliation.institute | Göttinger Graduiertenschule für Neurowissenschaften, Biophysik und molekulare Biowissenschaften (GGNB) | de |
| dc.subject.gokfull | Biologie (PPN619462639) | de |
| dc.description.embargoed | 2023-06-18 | de |
| dc.identifier.ppn | 1813924953 | |
| dc.notes.confirmationsent | Confirmation sent 2022-08-08T12:45:01 | de |